Protective effect of nicorandil on hypoxia‑induced apoptosis in HPAECs through inhibition of p38 MAPK phosphorylation

  • Authors:
    • Yanzhe Yu
    • Yonglong Xiao
    • Hui Wang
    • Junyang Li
    • Xiangrong Zuo
    • Hong Wang
    • Weiping Xie
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  • Published online on: January 2, 2013     https://doi.org/10.3892/mmr.2013.1255
  • Pages: 816-820
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Abstract

Endothelial cell apoptosis is induced under various conditions, including hypoxia, which is crucial for pulmonary hypertension. The present study aimed to investigate the protective effect of nicorandil against hypoxia‑induced apoptosis in human pulmonary arterial endothelial cells (HPAEC) and the potential mechanisms involved in the regulation of p38 mitogen‑activated protein kinase (MAPK). Following exposure to hypoxia for 24 h, 3‑(4,5‑dimethylthiazol‑2yl‑)‑2,5‑diphenyltetrazolium bromide assay was performed to measure cell viability. Annexin V‑propidium iodide double staining with flow cytometry and fluorescence staining of cells with Hoechst 33342 was then used to detect apoptosis. Expression of phosphorylated (phospho)‑p38 MAPK, Bcl‑2‑associated X protein, B‑cell lymphoma 2, caspase‑8, ‑9 and ‑3 and endothelial nitric oxide synthase (eNOS) was assayed by western blotting to investigate the mechanisms of action. Results showed that hypoxia significantly decreases cell viability by inducing cell apoptosis, while nicorandil and the p38 MAPK inhibitor, SB203580, reversed hypoxia‑induced apoptosis. Nicorandil and SB203580 consistently inhibited the phosphorylation of p38 MAPK and expression of various apoptosis‑related proteins induced by hypoxia. However, nicorandil increased the hypoxia‑induced downregulation of eNOS expression and the effects of nicorandil were completely blocked by the mitochondrial ATP‑sensitive potassium (mitoKATP) channel antagonist, 5‑hydroxydecanoate. Nicorandil was identified to protect HPAEC from hypoxia‑induced apoptosis by activating mitoKATP channels. The mechanisms by which this protective effect is mediated may involve inhibition of phospho‑p38 MAPK and downstream cell death pathways.
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March 2013
Volume 7 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Yu Y, Xiao Y, Wang H, Li J, Zuo X, Wang H and Xie W: Protective effect of nicorandil on hypoxia‑induced apoptosis in HPAECs through inhibition of p38 MAPK phosphorylation. Mol Med Rep 7: 816-820, 2013.
APA
Yu, Y., Xiao, Y., Wang, H., Li, J., Zuo, X., Wang, H., & Xie, W. (2013). Protective effect of nicorandil on hypoxia‑induced apoptosis in HPAECs through inhibition of p38 MAPK phosphorylation. Molecular Medicine Reports, 7, 816-820. https://doi.org/10.3892/mmr.2013.1255
MLA
Yu, Y., Xiao, Y., Wang, H., Li, J., Zuo, X., Wang, H., Xie, W."Protective effect of nicorandil on hypoxia‑induced apoptosis in HPAECs through inhibition of p38 MAPK phosphorylation". Molecular Medicine Reports 7.3 (2013): 816-820.
Chicago
Yu, Y., Xiao, Y., Wang, H., Li, J., Zuo, X., Wang, H., Xie, W."Protective effect of nicorandil on hypoxia‑induced apoptosis in HPAECs through inhibition of p38 MAPK phosphorylation". Molecular Medicine Reports 7, no. 3 (2013): 816-820. https://doi.org/10.3892/mmr.2013.1255